Statin drugs are 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor. These drugs competitively inhibit the synthesis of HMG-CoA reductase from endogenous cholesterol, consequently block the metabolic pathway of mevalonate in cells and then lower the cholesterol levels in cells. Thereby, the drugs stimulate and increase the quantity and activity of low density lipoprotein (LDL) receptor on the surface of cells (mainly for live cells), increase the removal rate of cholesterol from Serum, and thereby lower the cholesterol level. Statin drugs can inhibit the synthesis of apolipoprotein B-100 in the liver, thereby reducing the synthesis and secretion of triglyceride and lipoprotein. In addition to the regulation of blood lipids, statin drugs can inhibit the vascular endothelial of inflammatory response, stabilize atheromatous plaque and improve the function of vascular endothelial if they are used early in patients having acute coronary syndrome. Statin drugs are also useful in delaying the extent of atherosclerosis, anti-inflammatory, protection of nerve and antithrombotic.
Some effective statin drugs include lovastatin, simvastatin, pravastatin, mevastatin, fluvastatin, atorvastatin, cerivastatin, pitavastatin and rosuvastatin, etc.
There are many methods of the preparation of statins. For example, WO2002098854 discloses a method of synthesizing the trans-substituted olefin bonds of statin drugs by Julia-Kocienski olefination, comprising reacting chiral sulfone with an aldehyde of a hydrophobic anchor or residue of a HMG-CoA reductase inhibitor.
Although there are currently many methods of the preparing statins, there are still needs for new improved methods for preparing statins or statin intermediates in this field.